Expert Review of Proteomics

van Dijk, Anneke D.; de Bont, Eveline S. J. M.; Kornblau, Steven M.

doi: 10.1080/14789450.2020.1717951pmid: 31945303

Introduction: The biological heterogeneity of acute myeloid leukemia (AML) complicates personalized medicine. Individual prognosis is typically based on the presence of chromosomal and genetic lesions. Nevertheless, these classifications often lack a priori information about response to therapy. Since the protein expression landscape reflects the functional activity state of cells, we hypothesize that analyzing this can be used for the identification of protein activity markers to provide better risk stratification as well as may provide targeted therapeutic guidance in AML.Areas covered: Herein, we review recently new adopted drugs in the treatment for AML and discuss how quantitative proteomic techniques may contribute to better therapeutic selection in AML.Expert commentary: The net functional state of the cell is defined by the activity of protein within all the pathways that are active in the cell. Recognition of the proteomic profile of the leukemic blast could, therefore, complement current classification systems by providing a better a priori description of what pathways are important within a cell as a guide to the selection of therapy for the patient.

Cao, Wei-Qian; Liu, Ming-Qi; Kong, Si-Yuan; Wu, Meng-Xi; Huang, Zheng-Ze; Yang, Peng-Yuan

doi: 10.1080/14789450.2020.1708199pmid: 31914820

Introduction: Glycomics, which aims to define the glycome of a biological system to better assess the biological attributes of the glycans, has attracted increasing interest. However, the complexity and diversity of glycans present challenging barriers to glycome definition. Technological advances are major drivers in glycomics.Areas covered: This review summarizes the main methods and emphasizes the most recent advances in mass spectrometry-based methods regarding glycomics following the general workflow in glycomic analysis.Expert opinion: Recent mass spectrometry-based technological advances have significantly lowered the barriers in glycomics. The field of glycomics is moving toward both generic and precise analysis.

Yu, Hanjie; Shu, Jian; Li, Zheng

doi: 10.1080/14789450.2020.1720512pmid: 31971038

Introduction: Glycoproteomics is an important subdiscipline of proteomics, focusing on the role of protein glycosylation in various biological processes. Protein glycosylation is the enzymatic addition of sugars or oligosaccharides to proteins. Altered glycosylation often occurs in the early stages of disease development, for example, certain tumor-associated glycans have been shown to be expressed in precursor lesions of different types of cancer, making them powerful early diagnostic markers. Lectin microarrays have become a powerful tool for both the study of glycosylation and the diagnosis of various diseases including cancer.Areas covered: This review will discuss the most useful features of lectin microarrays, such as their technological advances, their capability for parallel/high-throughput analysis for the important glycopatterns of glycoprotein, and an overview of their use for glycosylation analysis of various complex protein samples, as well as their diagnostic potential in various diseases.Expert opinion: Lectin microarrays have proved to be useful in studying multiple lectin–glycan interactions in a single experiment and, with the advances made in the field, hold a promise of enabling glycopatterns of diseases in a fast and efficient manner. Lectin microarrays will become increasingly powerful early diagnostic tool for a variety of conditions.

Sheehan, David; McDonagh, Brian

doi: 10.1080/14789450.2020.1704260pmid: 31826671

Introduction: Protein thiols are susceptible to oxidation in health and disease. Redox proteomics methods facilitate the identification, quantification, and rationalization of oxidation processes including those involving protein thiols. These residues are crucial to understanding redox homeostasis underpinning normal cell functioning and regulation as well as novel biomarkers of pathology and promising novel drug targets.Areas covered: This article reviews redox proteomic approaches to study of protein thiols in some important human pathologies and assesses the clinical potential of individual Cys residues as novel biomarkers for disease detection and as targets for novel treatments.Expert commentary: Although protein thiols are not as routinely used as redox biomarkers as some other lesions such as carbonylation, there has been growing recent interest in their potential. Driven largely by developments in high-resolution mass spectrometry it is possible now to identify proteins that are redox modified at thiol groups or that interact with regulatory oxidoreductases. Thiols that are specifically susceptible to modification by reactive oxygen species can be routinely identified now and quantitative MS can be used to quantify the proportion of a protein that is redox modified.

Cantor, David I.; Cheruku, Harish R.; Westacott, Jack; Shin, Joo-Shik; Mohamedali, Abidali; Ahn, Seong Boem

doi: 10.1080/14789450.2020.1713103pmid: 31914823

Introduction: Despite advances in screening and treatment options, colorectal cancer (CRC) remains one of the most prevalent and lethal cancer subtypes. Resistance to cytotoxic or targeted therapy has remained a constant challenge to the treatment and long-term management of patients, attracting intense worldwide investigation since the 1950s. Through extensive investigations into the proteomic mechanisms and functions that convey resistance to therapy/s, researchers have become able to implicate alterations in several signaling pathways that provide and sustain resistance to treatment.Areas covered: In this review, we summarize how protein alterations are associated with resistance to therapy, with particular emphasis on CRC. An overview of the mechanisms of therapeutic resistance is described, highlighting recent studies which endeavor to elucidate the proteomic changes that are associated with the acquisition and promulgation of therapeutic resistance.Expert opinion: While cancers such as CRC have been intensively studied for decades, unresponsiveness and the resistance to therapy remain critical obstacles in the treatment of patients. Due to the inherent biological and clinical heterogeneity of individual CRCs, proteomic methods stand to become powerful tools to provide biological insights that may guide therapeutic strategies with the ultimate goal of refining emergent immunotherapeutic treatments.

Cid-Uribe, Jimena I.; Veytia-Bucheli, José Ignacio; Romero-Gutierrez, Teresa; Ortiz, Ernesto; Possani, Lourival D.

doi: 10.1080/14789450.2020.1705158pmid: 31834817

Introduction: A few scorpions are dangerous to humans. Their medical relevance was the initial driving force for venom research. By classical biochemistry and molecular cloning, several venom peptides and their coding transcripts were characterized, mainly those related to toxins. The discovery of other components with novel activities and potential applications has revitalized the interest in the field in the last decade and a half. Nontoxic scorpion species have also attracted major interest.Areas covered: Advances in the identification of scorpion venom components via high-throughput venomics (genomics, transcriptomics and proteomics) up to 2019 are summarized. A classification system for venom-related transcripts and proteins, together with an intuitive systematic nomenclature for RNAseq-generated transcripts are proposed. Venom components classified as Na+, K+, Ca2+, Cl− and TRP channel toxins, enzymes, protease inhibitors, host defense peptides and other peptidic molecules are briefly reviewed, giving a comprehensive picture of the venom.Expert opinion: Modern high-throughput technologies applied to scorpion venom studies have resulted in a dramatic increase in both, the number and diversity of available sequences, leading to a deeper understanding of the composition of scorpion venoms. Still, many newly-discovered venom constituents remain to be characterized, to complete the puzzle of scorpion venoms.

Arora, Naina; Raj, Anand; Anjum, Farhan; Kaur, Rimanpreet; Rawat, Suraj Singh; Kumar, Rajiv; Tripathi, Shweta; Singh, Gagandeep; Prasad, Amit

doi: 10.1080/14789450.2020.1719835pmid: 31968176

Background: Helminth infections cause widespread morbidity and are a significant global disease burden. One among them is Neurocysticercosis, a central nervous system infection caused by the larvae Taenia solium, leading to epilepsy. Helminths are strong immune modulators and can survive for a long time in adverse host environments. Kinases are molecular switches and are essential to initiate/propagate signaling cascades and are detrimental to the regulation of homeostasis. They have been implicated in the progression of many diseases and are potentially lucrative drug targets.Objective: To identify kinases in T. solium proteome and prioritize them as drug targets.Methodology: A Hidden Markov Model (HMM) was used to curate and classify kinases into families based on sequence homology to model organisms followed by phylogenetic analysis of each family. To predict potential drug targets, kinases were identified based on a homologically lethal relationship to C. elegans but non-lethal to humans. Kinases thus selected were searched for matching ligands in SARFkinase and DrugBank databases.Result and conclusion: T. solium kinases make up 1.8% of its proteome, CMGC is the largest kinase family and RGC is the smallest and catalytically inactive family. We predict 23-potential kinases to be drug targets for T. solium.